Human immunodeficiency virus (HIV) is the etiological agent of acquired immunodeficiency syndrome (AIDS). At present, there is no effective vaccine against this disease, and therapeutic agents provide only limited help. The objects of this project are to characterize HIV antigens, to determine the targets of humoral and cell-mediated immunity, and to use this information to develop candidate vaccines. We have constructed recombinant vaccinia viruses containing HIV genetic information. These viruses have been used as live experimental vaccines to immunize animals, to synthesize HIV proteins in tissue culture, to make targets for cytotoxic T cells, and to study CD4-envelope interactions. During the past year, a novel stable, soluble oligomeric form of the HIV-1 envelope protein was genetically engineered and purified. To test the immunogenicity of the protein, a large panel of approximately 150 monoclonal antibodies was made. A large proportion of the antibodies recognized conformational epitopes on the gp120 and gp41 portions of the envelope protein. This pattern was quite different from that obtained by monomeric envelope protein.